Neuronal CIPP (channel-interacting PDZ protein) is a multivalent PDZ protein that interacts with specific channels and receptors highly expressed in the brain. It is composed of four PDZ domains that behave as a scaffold to clusterize functionally connected proteins. In the present study, we selected a set of potential CIPP interactors that are involved directly or indirectly in mechanisms of cytoskeletal remodelling and membrane protrusion formation. For some of these, we first proved the direct binding to specific CIPP PDZ domains considered as autonomous elements, and then confirmed the interaction with the whole protein. In particular, the small G-protein effector IRSp53 (insulin receptor tyrosine kinase substrate protein p53) specifically interacts with the second PDZ domain of CIPP and, when co-transfected in cultured mammalian cells with a tagged full-length CIPP, it induces a marked reorganization of CIPP cytoplasmic localization. Large punctate structures are generated as a consequence of CIPP binding to the IRSp53 C-terminus. Analysis of the puncta nature, using various endocytic markers, revealed that they are not related to cytoplasmic vesicles, but rather represent multi-protein assemblies, where CIPP can tether other potential interactors.
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Research Article|
March 27 2009
Channel-interacting PDZ protein, ‘CIPP’, interacts with proteins involved in cytoskeletal dynamics
Emanuele Alpi;
Emanuele Alpi
1
*Cell and Developmental Biology Laboratory, Department of Biology, University of Pisa, 56010 Pisa, Italy
†Molecular Biology Laboratory, Scuola Normale Superiore, 56124 Pisa, Italy
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Elena Landi;
Elena Landi
1
*Cell and Developmental Biology Laboratory, Department of Biology, University of Pisa, 56010 Pisa, Italy
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Manuela Barilari;
Manuela Barilari
1
*Cell and Developmental Biology Laboratory, Department of Biology, University of Pisa, 56010 Pisa, Italy
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Michela Serresi;
Michela Serresi
‡NEST Scuola Normale Superiore and IIT, 56126 Pisa, Italy
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Piero Salvadori;
Piero Salvadori
§Department of Chemistry and Industrial Chemistry, University of Pisa, 56126 Pisa, Italy
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Angela Bachi;
Angela Bachi
∥Dibit2, San Raffaele Scientific Institute, 20132 Milano, Italy
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Luciana Dente
Luciana Dente
2
*Cell and Developmental Biology Laboratory, Department of Biology, University of Pisa, 56010 Pisa, Italy
2To whom correspondence should be addressed (email ldente@biologia.unipi.it).
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Publisher: Portland Press Ltd
Received:
July 08 2008
Revision Received:
November 03 2008
Accepted:
January 13 2009
Accepted Manuscript online:
January 13 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 419 (2): 289–300.
Article history
Received:
July 08 2008
Revision Received:
November 03 2008
Accepted:
January 13 2009
Accepted Manuscript online:
January 13 2009
Citation
Emanuele Alpi, Elena Landi, Manuela Barilari, Michela Serresi, Piero Salvadori, Angela Bachi, Luciana Dente; Channel-interacting PDZ protein, ‘CIPP’, interacts with proteins involved in cytoskeletal dynamics. Biochem J 15 April 2009; 419 (2): 289–300. doi: https://doi.org/10.1042/BJ20081387
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